The Immunology Core will provide assays of cellular immunity in support of this Program Project. The assays provided by the core will include the quantitation, immunophenotyping, and functional analyses of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) and CD4+ T helper cells. It will be important to have consistent measures of both the quantity and quality of the antigen-specific T cells so that the projects supported by this core modulating the immune response to CML will have useful immunology data to correlate with the measured clinical response(s). These measurements of immune status will be made on treated patients, some of which will be immuno-compromised, in the context of stem cell transplant patients both in the allogeneic and autologous setting (Project:Champlin), and in patients with Gleevec resistance (Project:Cortes). This core will also support the development of the methodology for the expansion and purification of PRl-specific CTL (Project:Molldrem), and the verification of immune function in transduced suicide T cells (Project:Kornblau). It will also be important to consider functional specific immunity in the context of how each patient's overall immune status and recovery is progressing. Therefore, in addition to monitoring CML-specific CTL, we will assay viral-specific T cells, examine the overall quantity and phenotype of the entire CD4 and CD8 T cell populations, and assess overall thymic function and T cell receptor (TCR) diversity. Specifically, the core will provide the following immune assays: 1) Assess the numbers and function of leukemia-specific T cells in patients with CML before and after immunotherapeutic interventions; 2) Assess the numbers and function of T cells specific for viral antigens important in infection prophylaxis in CML patients; 3) Systematically examine the impact of therapy for CML on the immunophenotypic composition of the naive and memory T cell repertoire; 4) Examine the role of thymic function on leukemia and viral specific T cells after stem cell transplant (SCT).